The Role And Mechanism Of ME1-Mediated Metabolic Reprogramming In Basal-like Breast Cancer

Breast cancer is one of the most common epitheligenic malignant tumor in females.There is an upward trend in the incidence of breast cancer in China.As a distinct molecular subtype of breast cancer,basal-like breast cancer(BLBC)is the most aggressive with poor prognosis due to lacking targeted therapy.The abnormal high expression of ME1(Malic enzymel)is found in various tumors,such as nasopharyngeal carcinoma and hepatocellular carcinoma.However,the role of ME1 in the progression of breast cancer is not yet clear.In this study,we identified the expression of ME1 in BLBC was much higher than that in other subtypes.Our experiments indicate impression of ME1 could make cells be more sensitive to deprived environment.MEl enhances proliferation of tumor cells under hypoxia conditions.Knockdown of ME1 also inhibited tumor growth.Additionally,we observed that ME1 enhanced adaptation of tumor cells to the innutritious and hypoxic environment.Interestingly,ME1 promoted the glucose consumption and lactate production,thus enhancing the glycolysis of tumor cells.In addition,ME1 reduced oxygen consumption of tumor cells.Thus,ME1 promote the shift fromoxidative phosphorylation to Warburg Effect,contributing the development of BLBC.Our results indicate that ME1 plays a crucial role in modulating breast cancer growth.Metabolic reprogramming mediated by ME1 has a profound impact on glucose metabolism and enhances breast cancer adaptation to hypoxia.Taken together,our study identifies ME1 as a key modulator of tumor aggressiveness has the potential to become a valuable therapeutic target for BLBC...